NLRC5 cooperates with the RFX transcription factor complex to induce MHC class I gene expression

• Published in: The Journal of immunology (1950) 2012-05, Vol.188 (10), p.4951-4958
• Main Authors: Meissner, Torsten B, Liu, Yuen-Joyce, Lee, Kyoung-Hee, Li, Amy, Biswas, Amlan, van Eggermond, Marja C J A, van den Elsen, Peter J, Kobayashi, Koichi S
• Format: Article
• Language: English
• Subjects: Activating Transcription Factor 1 - genetics; Activating Transcription Factor 1 - physiology; Amino Acid Motifs - genetics; Amino Acid Motifs - immunology; Cell Line; Cell Line, Tumor; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; HEK293 Cells; HLA-B Antigens - biosynthesis; HLA-B Antigens - genetics; Humans; Intracellular Signaling Peptides and Proteins - physiology; Multigene Family; Promoter Regions, Genetic; Regulatory Factor X Transcription Factors; Regulatory Sequences, Nucleic Acid - immunology; Transcription Factors - genetics; Transcription Factors - physiology; Transcriptional Activation - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1103160

Tight regulation of MHC class I gene expression is critical for CD8 T cell activation and host adaptive-immune responses. The promoters of MHC class I genes contain a well-conserved core module, the W/S-X-Y motif, which assembles a nucleoprotein complex termed MHC enhanceosome. A member of the nucleotide-binding domain, leucine-rich repeat (NLR) protein family, NLRC5, is a newly identified transcriptional regulator of MHC class I genes. NLRC5 associates with and transactivates the proximal promoters of MHC class I genes, although the molecular mechanism of transactivation has not been understood. In this article, we show that NLRC5-mediated MHC class I gene induction requires the W/S and X1, X2 cis-regulatory elements. The transcription factors RFX5, RFXAP, and RFXANK/B, which compose the RFX protein complex and associate with the X1 box, cooperate with NLRC5 for MHC class I expression. Coimmunoprecipitation experiments revealed that NLRC5 specifically interacts with the RFX subunit RFXANK/B via its ankyrin repeats. In addition, we show that NLRC5 can cooperate with ATF1 and the transcriptional coactivators CBP/p300 and general control nonderepressible 5, which display histone acetyltransferase activity. Taken together, our data suggest that NLRC5 participates in an MHC class I-specific enhanceosome, which assembles on the conserved W/S-X-Y core module of the MHC class I proximal promoters, including the RFX factor components and CREB/ATF1 family transcription factors, to promote MHC class I gene expression.